Auto-antibodies against such lipids as cholesterol [Swartz G. M., Jr., et al Proc. Natl. Acad. Sci. USA (1988), 85, 1902–1906, Alving C. R. and Swartz G. M., Jr. Critical Reviews in Immunology (1991), 10, 441–453.], phospholipids [Alving C. R. Biochem. Soc. Trans. (1984), 12, 342–344.] and low density lipoproteins (LDL) are found in human plasma [Kabakov A. E. et al Clin. Immun. Immunopath. (1992), 63, 214–220, Mironova M et al Ibid. (1997), 85, 73–82.] and are involved in the development of atherosclerosis [Lopes-Virella M. F. and Virella G. Clin. Immun. Immunopath. (1994), 73, 155–167, Kiener P. A. et al Arterioscler. Thromb Vasc. Biol. (1995), 15, 990–999.].
Separately, neither antibodies nor LDL are a pathogenic factor, only the immune complex of the two [Tertov V. V et al Atherosclerosis (1990), 81, 183–189, Orekhov A. N. et al Biochem. Biophys. Res. Comm. (1989), 162, 206–211.].
Immune complexes comprising unmodified plasma lipoproteins are known to have a low atherogenicity. However, if the lipoproteins become modified, in particular oxidised, these immune complexes become highly atherogenic [Orekhov A. N. et al Biobhem. Biophys. Res. Comm. (1989), 162, 206–211, Orekhov A. N. et al Arterioscler. Thromb. Vasc. Biol. (1991), 11, 316–326.] Oxidation of plasma lipids, which takes the form of peroxidation, is generally considered to be responsible for the development of atherosclerosis and is a consistently observed and published feature of this disease in the clinic [Goto Y. In: Lipid Peroxides in Biology and Medicine, Ed. Yagi K., Academic Press, New York, London, Tokyo (1982), 295–303, Halliwell D. and J. M. C. Gutteridge, Free Radicals in Biology and Medicine, Clarendon Press, Oxford, 1989, Schultz D et al Arterioscler. Thromb. Vasc. Biol. (2000), 20, 1412–1413]. However, until the present disclosure, the cause of this peroxidation in plasma was obscure.